| 1. |
- Rajewsky, N., et al.
(författare)
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LifeTime and improving European healthcare through cell-based interceptive medicine
- 2020
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 587:7834, s. 377-386
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Tidskriftsartikel (refereegranskat)abstract
- LifeTime aims to track, understand and target human cells during the onset and progression of complex diseases and their response to therapy at single-cell resolution. This mission will be implemented through the development and integration of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during progression from health to disease. Analysis of such large molecular and clinical datasets will discover molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. Timely detection and interception of disease embedded in an ethical and patient-centered vision will be achieved through interactions across academia, hospitals, patient-associations, health data management systems and industry. Applying this strategy to key medical challenges in cancer, neurological, infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.
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| 2. |
- Callaway, EM, et al.
(författare)
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A multimodal cell census and atlas of the mammalian primary motor cortex
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 598:7879, s. 86-102
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Tidskriftsartikel (refereegranskat)abstract
- Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.
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| 3. |
- Pelletier, F., et al.
(författare)
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Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C
- 2021
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Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 106:2
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Tidskriftsartikel (refereegranskat)abstract
- Context: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. Objective: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. Design: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. Setting: This was a multicenter retrospective study using information collected from 3 predominant centers. Patients: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. Main Outcome Measures: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. Results: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. Conclusions: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder.
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| 4. |
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| 5. |
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| 6. |
- Sieber, Maximilian, et al.
(författare)
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Wear-resistant coatings on aluminium produced by plasma anodising - A correlation of wear properties, microstructure, phase composition and distribution
- 2014
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Ingår i: Surface & Coatings Technology. - : Elsevier. - 0257-8972 .- 1879-3347. ; 240, s. 96-102
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Tidskriftsartikel (refereegranskat)abstract
- In the recent decades, various process windows have been found for plasma anodising of aluminium surfaces to produce wear-resistant alumina coatings. The coatings offer a high hardness and provide an excellent bonding to the substrate material, thus preventing spallation under mechanical or tribological load. In the present study, coatings with a high abrasive wear resistance and a hardness of up to 12GPa were produced in an electrolyte of 5g/l sodium metasilicate and 5g/l potassium hydroxide at a current density of 30A/dm2. To understand the reasons for the high wear resistance, the morphology as well as the phase composition and distribution within the coating were examined globally and locally using X-ray diffraction with conventional and grazing incidence and electron backscatter diffraction. The analyses show that the coating globally is comprised of approximately one third of α-alumina, one third of γ-alumina and one third of amorphous alumina with locally varying phase content.
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| 7. |
- Went, M, et al.
(författare)
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Author Correction: Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 213-
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Tidskriftsartikel (refereegranskat)abstract
- The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.
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| 8. |
- Da Silva Filho, M. I., et al.
(författare)
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Genome-wide association study of immunoglobulin light chain amyloidosis in three patient cohorts : Comparison with myeloma
- 2017
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 0887-6924 .- 1476-5551. ; 31:8, s. 1735-1742
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Tidskriftsartikel (refereegranskat)abstract
- Immunoglobulin light chain (AL) amyloidosis is characterized by tissue deposition of amyloid fibers derived from immunoglobulin light chain. AL amyloidosis and multiple myeloma (MM) originate from monoclonal gammopathy of undetermined significance. We wanted to characterize germline susceptibility to AL amyloidosis using a genome-wide association study (GWAS) on 1229 AL amyloidosis patients from Germany, UK and Italy, and 7526 healthy local controls. For comparison with MM, recent GWAS data on 3790 cases were used. For AL amyloidosis, single nucleotide polymorphisms (SNPs) at 10 loci showed evidence of an association at P<10 -5 with homogeneity of results from the 3 sample sets; some of these were previously documented to influence MM risk, including the SNP at the IRF4 binding site. In AL amyloidosis, rs9344 at the splice site of cyclin D1, promoting translocation (11;14), reached the highest significance, P=7.80 × 10 -11; the SNP was only marginally significant in MM. SNP rs79419269 close to gene SMARCD3 involved in chromatin remodeling was also significant (P=5.2 × 10 -8). These data provide evidence for common genetic susceptibility to AL amyloidosis and MM. Cyclin D1 is a more prominent driver in AL amyloidosis than in MM, but the links to aggregation of light chains need to be demonstrated.
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| 9. |
- Humbert, F., et al.
(författare)
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Longitudinal and Transverse-Momentum Distributions of Li-9 Fragments from Break-up of Li-11
- 1995
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 347:3-4, s. 198-204
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Tidskriftsartikel (refereegranskat)abstract
- Transverse and longitudinal momentum distributions of Li-9 fragments from Li-11 break-up reactions in C, Al and Pb targets have been measured at 280 MeV/u. The two-neutron removal cross-section was measured to be sigma(-2n), = 0.26 +/- 0.02 b for the carbon target, sigma(-2n) = 0.47 +/- 0.08 b for the aluminum target and sigma(-2n), = 1.9 +/- 0.4 b for the lead target. No significant difference is observed between the narrow widths (FWHM approximate to 47 MeV/c) of the transverse and longitudinal momentum distributions of the Li-9 fragments. The physical implications of this are discussed.
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| 10. |
- Johnson, D C, et al.
(författare)
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Genetic factors influencing the risk of multiple myeloma bone disease.
- 2016
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Ingår i: Leukemia. - : Springer Science and Business Media LLC. - 1476-5551 .- 0887-6924. ; 30, s. 883-888
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Tidskriftsartikel (refereegranskat)abstract
- A major complication of multiple myeloma (MM) is the development of osteolytic lesions, fractures and bone pain. To identify genetic variants influencing the development of MM bone disease (MBD), we analyzed MM patients of European ancestry (totalling 3774) which had been radiologically surveyed for MBD. Each patient had been genotyped for ~600 000 SNPs with genotypes for six million common variants imputed using 1000Genomes Project and UK10K as reference. We identified a locus at 8q24.12 for MBD (rs4407910, OPG/TNFRSF11B, odds ratio [OR]=1.38, P=4.09 × 10(-9)) and a promising association at 19q13.43 (rs74676832, OR=1.97, P=9.33 × 10(-7)). Our findings demonstrate that germline variation influences MBD and highlights the importance of RANK/RANKL/OPG pathway in MBD development. These findings will contribute to the development of future strategies for prevention of MBD in the early precancerous phases of MM.Leukemia accepted article preview online, 16 December 2015. doi:10.1038/leu.2015.342.
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| 11. |
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| 12. |
- Nilsson, Thomas, 1965, et al.
(författare)
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He-6 and neutron momentum distributions from He-8 in nuclear break-up reactions at 240 MeV/u
- 1996
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Ingår i: Nuclear Physics A. - 0375-9474. ; 598:3, s. 418-434
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Tidskriftsartikel (refereegranskat)abstract
- Neutron and He-6 momentum distributions from He-8 break-up reactions in a C target have been measured at 240 MeV/u. The two-neutron removal cross section was found to be sigma(-2n) = 0.27 +/- 0.03 b. The nature of the momentum distributions is interpreted in some simple reaction scenarios.
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| 13. |
- Nilsson, Thomas, 1965, et al.
(författare)
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Neutron Momentum Distributions from Core Break-up Reactions of Halo Nuclei
- 1995
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Ingår i: Europhysics Letters. - 0295-5075 .- 1286-4854. ; 30:1, s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- Neutron angular distributions from violent break-up reactions of Li-11 and Be-11 have been measured at 28 MeV/u and 280 MeV/u and at 41 MeV/u and 460 MeV/u, respectively. The derived neutron momentum distributions show a narrow component in transverse momentum that is within uncertainties independent of beam energy and target charge. This component is suggested to be simply related to the momentum distribution of the loosely bound halo neutron(s) in the projectiles.
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| 14. |
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| 15. |
- Suliman, S., et al.
(författare)
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Nanodiamond modified copolymer scaffolds affects tumour progression of early neoplastic oral keratinocytes
- 2016
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Ingår i: Biomaterials. - : Elsevier. - 0142-9612 .- 1878-5905. ; 95, s. 11-21
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to evaluate the tumorigenic potential of functionalising poly(LLA-co-CL) scaffolds. The copolymer scaffolds were functionalised with nanodiamonds (nDP) or with nDP and physisorbed BMP-2 (nDP-PHY) to enhance osteoinductivity. Culturing early neoplastic dysplastic keratinocytes (DOKLuc) on nDP modified scaffolds reduced significantly their subsequent sphere formation ability and decreased significantly the cells' proliferation in the supra-basal layers of in vitro 3D oral neoplastic mucosa (3D-OT) when compared to DOKLuc previously cultured on nDP-PHY scaffolds. Using an in vivo non-invasive environmentally-induced oral carcinogenesis model, nDP scaffolds were observed to reduce bioluminescence intensity of tumours formed by DOKLuc + carcinoma associated fibroblasts (CAF). nDP modification was also found to promote differentiation of DOKLuc both in vitro in 3D-OT and in vivo in xenografts formed by DOKLuc alone. The nDP-PHY scaffold had the highest number of invasive tumours formed by DOKLuc + CAF outside the scaffold area compared to the nDP and control scaffolds. In conclusion, in vitro and in vivo results presented here demonstrate that nDP modified copolymer scaffolds are able to decrease the tumorigenic potential of DOKLuc, while confirming concerns for the therapeutic use of BMP-2 for reconstruction of bone defects in oral cancer patients due to its tumour promoting capabilities.
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| 16. |
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| 17. |
- Aleksandrov, D., et al.
(författare)
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Halo excitations in fragmentation of He-6 at 240 MeV/u on carbon and lead targets
- 2000
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Ingår i: Nuclear Physics A. - 0375-9474. ; 669:1-2, s. 51-64
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Tidskriftsartikel (refereegranskat)abstract
- Dissociation of a 240 MeV/u beam of He-6, incident on carbon and lead targets, has been studied in kinematically complete experiments to investigate low-lying excitation modes in the halo nucleus He-6. It is shown that alignment effects characterize the inelastic scattering and allow an unambiguous assignment of the spin of a narrow resonance observed in the excitation energy spectrum. The differential cross sections for the He-6 inelastic scattering on carbon and lead targets were deduced from the measured moments of the two neutrons and the a-particle. An analysis of these distributions shows that quadrupole and, possibly, monopole excitations characterize the hadronic interaction, while the dipole mode is dominating in Coulomb dissociation. Neither theoretically predicted new resonance states in He-6 nor nuclear excitation of a dipole mode were found. Direct evidence has been obtained for strong suppression of Coulornb post-acceleration in direct Coulomb breakup in a lead target.
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| 18. |
- Aleksandrov, D., et al.
(författare)
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Invariant mass spectrum and alpha-n correlation function studied in the fragmentation of He-6 on a carbon target
- 1998
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Ingår i: Nuclear Physics A. - 0375-9474. ; 633:2, s. 234-246
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Tidskriftsartikel (refereegranskat)abstract
- Momentum distributions and invariant mass spectra from the breakup of He-6 ions with an energy of 240 MeV/u interacting with a carbon target have been studied. The data were used to extract information about the reaction mechanism which is influenced by the structure of He-6. It is found that the dominant reaction mechanism is a two-step process: knock out of one neutron followed by the decay of the He-5 resonance. The shape of the (alpha+n) two-body invariant mass spectrum is interpreted as mainly reflecting the 5He ground state which is a J(pi) = 3/2(-) resonance. However, no evidence for correlations between cu particles and neutrons is observed in the momentum widths of the distributions. It is demonstrated that a combined analysis of the two-body invariant mass spectrum and an appropriate correlation function may be used to determine the properties of the intermediate resonance. (C) 1998 Elsevier Science B.V.
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| 19. |
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| 20. |
- Auffray, Charles, et al.
(författare)
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Making sense of big data in health research: Towards an EU action plan
- 2016
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Ingår i: Genome Medicine. - : BIOMED CENTRAL LTD. - 1756-994X. ; 8:71
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Tidskriftsartikel (refereegranskat)abstract
- Medicine and healthcare are undergoing profound changes. Whole-genome sequencing and high-resolution imaging technologies are key drivers of this rapid and crucial transformation. Technological innovation combined with automation and miniaturization has triggered an explosion in data production that will soon reach exabyte proportions. How are we going to deal with this exponential increase in data production? The potential of "big data" for improving health is enormous but, at the same time, we face a wide range of challenges to overcome urgently. Europe is very proud of its cultural diversity; however, exploitation of the data made available through advances in genomic medicine, imaging, and a wide range of mobile health applications or connected devices is hampered by numerous historical, technical, legal, and political barriers. European health systems and databases are diverse and fragmented. There is a lack of harmonization of data formats, processing, analysis, and data transfer, which leads to incompatibilities and lost opportunities. Legal frameworks for data sharing are evolving. Clinicians, researchers, and citizens need improved methods, tools, and training to generate, analyze, and query data effectively. Addressing these barriers will contribute to creating the European Single Market for health, which will improve health arid healthcare for all Europearis.
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| 21. |
- Barthel, Roland, 1967, et al.
(författare)
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An integrated modelling framework for simulating regional-scale actor responses to global change in the water domain
- 2008
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Ingår i: Environmental Modelling & Software. - : Elsevier BV. - 1364-8152. ; 23:9, s. 1095-1121
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Tidskriftsartikel (refereegranskat)abstract
- Within coupled hydrological simulation systems, taking socio-economic processes into account is still a challenging task. In particular, systems that aim at evaluating impacts of climatic change on large spatial and temporal scales cannot be based on the assumption that infrastructure, economy, demography and other human factors remain constant while physical boundary conditions change. Therefore, any meaningful simulation of possible future scenarios needs to enable socio-economic systems to react and to adapt to climatic changes. To achieve this it is necessary to simulate decision-making processes of the relevant actors in a way which is adequate for the scale, the catchment specific management problems to be investigated and finally the data availability. This contribution presents the DEEPACTOR approach for representing such human decision processes, which makes use of a multi-actor simulation framework and has similarities to agent-based approaches. This DEEPACTOR approach is embedded in DANUBIA, a coupled simulation system comprising 16 individual models to simulate Global Change impacts on the entire water cycle of the Upper Danube Catchment (Germany, 77,000 km(2)). The applicability of DANUBIA and in particular the DEEPACTOR approach for treating the socio-economic part of the water cycle in a process-based way is demonstrated by means of concrete simulation models of the water supply sector and of the domestic water users. Results from scenario simulations are used to demonstrate the capabilities and limitations of the approach. (c) 2008 Elsevier Ltd. All rights reserved.
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| 22. |
- Barthel, Roland, 1967, et al.
(författare)
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Linking the physical and the socio-economic compartments of an integrated water and land use management model on a river basin scale using an object-oriented water supply model
- 2005
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Ingår i: Physics and Chemistry of the Earth. - : Elsevier BV. - 1474-7065. ; 30:6-7, s. 389-397
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Tidskriftsartikel (refereegranskat)abstract
- Within the framework of the research project 'GLOWA-Danube', a model of the water supply sector has been developed. GLOWA-Danube investigates long-term changes in the water cycle of the Upper Danube river basin in light of global change. For this purpose, the decision support system DANUBIA, comprising 15 fully coupled models, has been developed. Within DANUBIA the water supply model ('WaterSupply') forms the link between various physical models determining water quality and availability and several socio-economic models determining water consumption and demand. Having a central focus on public drinking water supply, its purpose is to correctly simulate the present day system of water extraction and distribution and the related costs, but also to allow meaningful response to possible future changes of boundary conditions, first and foremost changes in water demand or water availability and quality. Response mechanisms are also envisioned for changes in political and economic boundary conditions, and advances in technology. The model will be used locate critical regions which could experience water stress in the future, but does not aim to find the appropriate solutions or to predict the optimal organisation of water supply in the Danube Basin under such changing conditions. In the object-oriented model structure, both water supply companies (WSC) and communities are represented by main classes. Both classes have a limited view and knowledge of their environment. A community knows where and how much water is consumed and from which WSC it is served. A WSC possesses information regarding extraction sites and water rights, raw water quality and potential collaborating WSC. The WSC can perform actions that are different from 'business as usual'. These deviations from their usual behaviour can be interpreted by decision makers but should not be regarded as a replacement for the decision-making process itself. The model is conceptualised using object-oriented concepts of the Unified Modelling Language (UML) and is implemented in JAVA. This short overview is meant to answer key questions such as why and how WaterSupply was implemented, what is unique and new about the model and what are the general lessons learned and the added value with regard to integrated modelling on a river basin scale. It is obvious that in the attempt to answer these questions it is not possible to satisfy experts from all the relevant related fields, which include computer sciences, economy, behavioural science and not least water supply engineering and hydrology. (c) 2005 Elsevier Ltd. All rights reserved.
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| 23. |
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| 24. |
- Barthel, Roland, 1967, et al.
(författare)
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Using the multiactor-approach in GLOWA-danube to simulate decisions for the water supply sector under conditions of global climate change
- 2010
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Ingår i: Water Resources Management. - : Springer Science and Business Media LLC. - 0920-4741 .- 1573-1650. ; 24:2, s. 239-275
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Tidskriftsartikel (refereegranskat)abstract
- Glowa-Danube (www.glowa-danube.de) is an interdisciplinary project that aims to develop integrated strategies and tools for water and land use management in the upper Danube catchment (Germany, Austria ~77,000 km2). The project is one of five within the Glowa research program (www.glowa.org) dealing with Global Change effects on the water cycle in six meso-scale catchments (up to 100,000 km2) in Central Europe, West Africa and the Middle East. In the Glowa-Danube project, 16 natural science and socio-economic simulation models are integrated in the coupled simulation system Danubia. This article describes the underlying concept and implementation of WaterSupply, a multiactor-based model of the water supply sector with a focus on water resource utilization and distribution of individual water supply companies. Within Danubia, WaterSupply represents the link between water supply and demand, where the former is simulated by a groundwater and a surface water model and the latter by water consumption models of four different sectors (domestic, industrial, agricultural and tourism). WaterSupply interprets the quantitative state of water resources for defined spatial and temporal units according to sustainability requirements and assesses the state of resources in relation to present water supply schemes and the dynamics of user demand. WaterSupply then seeks both to optimize the resource use of supply companies and to identify critical regions for which further adaptation of the water supply scheme will become necessary under changing climatic conditions. In this article, a brief description of the Glowa-Danube project and the integrated simulation system Danubia is followed by a short presentation of the DeepActor framework, which provides a common conceptual and technical basis for the socio-economic simulation models of Glowa-Danube. The main body of the article is devoted to the concept, the implementation and simulation results of WaterSupply. Results from different scenario calculations demonstrate the capabilities and the potential fields of application of the model. © Springer Science+Business Media B.V. 2009.
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| 25. |
- Baumann, T., et al.
(författare)
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Longitudinal momentum distributions of C-16,C-18 fragments after one-neutron removal from C-17,C-19
- 1998
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Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - 0370-2693. ; 439:3-4, s. 256-261
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Tidskriftsartikel (refereegranskat)abstract
- The fragment separator FRS at GSI was used as an energy-loss spectrometer to measure the longitudinal momentum distributions of C-16,C-18 fragments after one-neutron removal reactions in C-17,C-19 impinging on a carbon target at about 910 MeV/u. The distributions in the projectile frames are characterized by a FWHM of 141 +/- 6 MeV/c for C-16 and 69 +/- 3 MeV/c for C-18. Th, results are compared with experimental data obtained at lower energies and discussed within existing theoretical models. (C) 1998 Elsevier Science B.V. AU rights reserved.
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